Department of Cardiology, Central Hospital of Baoji City, Shannxi Province 721008, P.R. China.
Biosci Rep. 2020 Jan 31;40(1). doi: 10.1042/BSR20191000.
MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.
微小 RNA 在急性心肌梗死 (AMI) 的调控和病理生理学中发挥重要作用。本研究旨在评估 miR-206 在 AMI 大鼠心脏中的表达特征及其相应的分子机制。与非梗死区相比,miR-206 在梗死心肌区和缺氧诱导的心肌细胞中的表达显著降低。miR-206 的过表达可减少体外心肌细胞凋亡,而 miR-206 的下调则增加心肌细胞凋亡。此外,miR-206 在体内过表达可显著减少大鼠心脏的心肌梗死面积和心肌细胞凋亡。我们发现 miR-206 对心肌细胞凋亡具有保护作用,与其靶蛋白酪氨酸磷酸酶 1B (PTP1B) 有关。miR-206 的功能获得抑制 PTP1B 的表达,miR-206 的功能缺失则上调 PTP1B 的表达。此外,PTP1B 的过表达可显著增加心肌细胞凋亡。这些结果共同表明,miR-206 通过靶向 PTP1B 对 AMI 诱导的心肌细胞凋亡具有保护作用。